Submissions for variant NM_004064.5(CDKN1B):c.326T>A (p.Val109Asp)

dbSNP: rs2066827

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000460482	SCV000377013	likely benign	Multiple endocrine neoplasia type 4	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000460482	SCV000554683	likely benign	Multiple endocrine neoplasia type 4	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001019555	SCV001180929	benign	Hereditary cancer-predisposing syndrome	2022-04-28	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Sema4, Sema4	RCV001019555	SCV002535483	benign	Hereditary cancer-predisposing syndrome	2022-03-16	criteria provided, single submitter	curation
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000460482	SCV002584732	uncertain significance	Multiple endocrine neoplasia type 4	2022-07-12	criteria provided, single submitter	clinical testing	The CDKN1B c.326T>A (p.Val109Asp) missense change has a maximum subpopulation frequency of 0.099% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with multiple endocrine neoplasia type 4. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477882	SCV004220755	likely benign	not provided	2022-03-14	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003897706	SCV004710354	likely benign	CDKN1B-related disorder	2022-04-26	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).